Definition of an eXecutable SPEM 2.0

International audienceOne major advantage of executable models is that once constructed, they can be run, checked, validated and improved in short incremental and iterative cycles. In the field of Software Process Modeling, process models have not yet reached the level of precision that would allow their execution. Recently the OMG issued a new revision of its standard for Software Process Modeling, namely SPEM2.0. However, even if executability was defined as a mandatory requirement in the RFP (Request For Proposal), the adopted specification does not fulfill it. This paper presents a critical analysis on the newly defined standard and addresses its lacks in terms of executability. An approach is proposed in order to extend the standard with a set of concepts and behavioural semantics that would allow SPEM2.0 process models to be checked through a mapping to Petri nets and monitored through a transformation into BPEL

Mindfulness-Based Reduction Stress Reduction for Patients with Rheumatoid Arthritis and Depressive Symptoms: a Pilot Trial

Background : Despite their efficacy at controlling joint inflammation, current treatments of rheumatoid arthritis (RA) leave up to 40% of patients into non-remission. Non-remission, frequently due to persistently negative self-reported impact of RA, was found to be associated with significant persistent depressive symptoms 6-7 months after initiation of arthritis treatment. Mindfulness-Based Stress Reduction (MBSR) is proposed to improve depressive symptoms and RA-related clinical outcomes. To pave the way for an eventual randomized controlled trial, a feasibility and acceptability study of MBSR has been realized. Methods: A standardized 8-week MBSR program was offered to groups of patients with controlled inflammatory disease but high levels of depressive symptoms.Qualitative interviews based on a theoretical framework of acceptability were conducted. Change in depressive symptoms (CES-D tool), fatigue and pain (SF-36), anxiety (GAD-7), pain, disease activity (PtVAS and SDAI scores) was measured over a 6-month period. Results: 27 patients have been recruited (3 distinct MBSR groups). Factors leading to a higher rate of success in recruitment were identified. Despite the small sample, the intervention was found to have a clear impact on depressive symptoms (p=0.004), anxiety (p=0.005), and social functioning (from the SF-36; p=0.04). Patients reported that MBSR gave them the opportunity to control their reactions in face of stressful situations.Perceptions were almost uniformly positive towards MBSR, and most appear to have integrated some part of the intervention in their daily life. Conclusions: Although recruitment was challenging, a MBSR trial on depressed patients with controlled inflammatory disease was found acceptable and feasible within this population. Preliminary clinical results showed positive impacts of such intervention. 

A Type System for Privacy Properties (Technical Report)

Mature push button tools have emerged for checking trace properties (e.g. secrecy or authentication) of security protocols. The case of indistinguishability-based privacy properties (e.g. ballot privacy or anonymity) is more complex and constitutes an active research topic with several recent propositions of techniques and tools. We explore a novel approach based on type systems and provide a (sound) type system for proving equivalence of protocols, for a bounded or an unbounded number of sessions. The resulting prototype implementation has been tested on various protocols of the literature. It provides a significant speed-up (by orders of magnitude) compared to tools for a bounded number of sessions and complements in terms of expressiveness other state-of-the-art tools, such as ProVerif and Tamarin: e.g., we show that our analysis technique is the first one to handle a faithful encoding of the Helios e-voting protocol in the context of an untrusted ballot box

Pixelated microfluidics for drug screening on tumour spheroids and ex vivo microdissected tumour explants

ABSTRACT: Anticancer drugs have the lowest success rate of approval in drug development programs. Thus, preclinical assays that closely predict the clinical responses to drugs are of utmost importance in both clinical oncology and pharmaceutical research. 3D tumour models preserve the tumoral architecture and are cost- and time-efficient. However, the short-term longevity, limited throughput, and limitations of live imaging of these models have so far driven researchers towards less realistic tumour models such as monolayer cell cultures. Here, we present an open-space microfluidic drug screening platform that enables the formation, culture, and multiplexed delivery of several reagents to various 3D tumour models, namely cancer cell line spheroids and ex vivo primary tumour fragments. Our platform utilizes a microfluidic pixelated chemical display that creates isolated adjacent flow sub-units of reagents, which we refer to as fluidic ‘pixels’, over tumour models in a contact-free fashion. Up to nine different treatment conditions can be tested over 144 samples in a single experiment. We provide a proof-of-concept application by staining fixed and live tumour models with multiple cellular dyes. Furthermore, we demonstrate that the response of the tumour models to biological stimuli can be assessed using the platform. Upscaling the microfluidic platform to larger areas can lead to higher throughputs, and thus will have a significant impact on developing treatments for cancer

Structural insights into chaperone addiction of toxin-antitoxin systems

International audienceSecB chaperones assist protein export by binding both unfolded proteins and the SecA motor. Certain SecB homologs can also control toxin-antitoxin (TA) systems known to modulate bacterial growth in response to stress. In such TA-chaperone (TAC) systems, SecB assists the folding and prevents degradation of the antitoxin, thus facilitating toxin inhibition. Chaperone dependency is conferred by a C-terminal extension in the antitoxin known as chaperone addiction (ChAD) sequence, which makes the antitoxin aggregation-prone and prevents toxin inhibition. Using TAC of Mycobacterium tuberculosis, we present the structure of a SecB-like chaperone bound to its ChAD peptide. We find differences in the binding interfaces when compared to SecB–SecA or SecB-preprotein complexes, and show that the antitoxin can reach a functional form while bound to the chaperone. This work reveals how chaperones can use discrete surface binding regions to accommodate different clients or partners and thereby expand their substrate repertoire and functions

Cross-validation of ELISA and a portable surface plasmon resonance instrument for IgG antibody serology with SARS-CoV-2 positive individuals.

We report on the development of surface plasmon resonance (SPR) sensors and matching ELISAs for the detection of nucleocapsid and spike antibodies specific to the novel coronavirus 2019 (SARS-CoV-2) in human serum, plasma and dried blood spots (DBS)

Le Forum, Vol. 42 No. 1

https://digitalcommons.library.umaine.edu/francoamericain_forum/1094/thumbnail.jp

Strategies and impacts of patient and family engagement in collaborative mental healthcare: protocol for a systematic and realist review

INTRODUCTION: Collaborative mental healthcare (CMHC) has garnered worldwide interest as an effective, team-based approach to managing common mental disorders in primary care. However, questions remain about how CMHC works and why it works in some circumstances but not others. In this study, we will review the evidence on one understudied but potentially critical component of CMHC, namely the engagement of patients and families in care. Our aims are to describe the strategies used to engage people with depression or anxiety disorders and their families in CMHC and understand how these strategies work, for whom and in what circumstances. METHODS AND ANALYSIS: We are conducting a review with systematic and realist review components. Review part 1 seeks to identify and describe the patient and family engagement strategies featured in CMHC interventions based on systematic searches and descriptive analysis of these interventions. We will use a 2012 Cochrane review of CMHC as a starting point and perform new searches in multiple databases and trial registers to retrieve more recent CMHC intervention studies. In review part 2, we will build and refine programme theories for each of these engagement strategies. Initial theory building will proceed iteratively through content expert consultations, electronic searches for theoretical literature and review team brainstorming sessions. Cluster searches will then retrieve additional data on contexts, mechanisms and outcomes associated with engagement strategies, and pairs of review authors will analyse and synthesise the evidence and adjust initial programme theories. ETHICS AND DISSEMINATION: Our review follows a participatory approach with multiple knowledge users and persons with lived experience of mental illness. These partners will help us develop and tailor project outputs, including publications, policy briefs, training materials and guidance on how to make CMHC more patient-centred and family-centred

The CADM1 tumor suppressor gene is a major candidate gene in MDS with deletion of the long arm of chromosome 11.

Myelodysplastic syndromes (MDS) represent a heterogeneous group of clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis leading to peripheral cytopenias and in a substantial proportion of cases to acute myeloid leukemia. The deletion of the long arm of chromosome 11, del(11q), is a rare but recurrent clonal event in MDS. Here, we detail the largest series of 113 cases of MDS and myelodysplastic syndromes/myeloproliferative neoplasms (MDS/MPN) harboring a del(11q) analyzed at clinical, cytological, cytogenetic, and molecular levels. Female predominance, a survival prognosis similar to other MDS, a low monocyte count, and dysmegakaryopoiesis were the specific clinical and cytological features of del(11q) MDS. In most cases, del(11q) was isolated, primary and interstitial encompassing the 11q22-23 region containing ATM, KMT2A, and CBL genes. The common deleted region at 11q23.2 is centered on an intergenic region between CADM1 (also known as Tumor Suppressor in Lung Cancer 1) and NXPE2. CADM1 was expressed in all myeloid cells analyzed in contrast to NXPE2. At the functional level, the deletion of Cadm1 in murine Lineage-Sca1+Kit+ cells modifies the lymphoid-to-myeloid ratio in bone marrow, although not altering their multilineage hematopoietic reconstitution potential after syngenic transplantation. Together with the frequent simultaneous deletions of KMT2A, ATM, and CBL and mutations of ASXL1, SF3B1, and CBL, we show that CADM1 may be important in the physiopathology of the del(11q) MDS, extending its role as tumor-suppressor gene from solid tumors to hematopoietic malignancies

Double threading through DNA: NMR structural study of a bis-naphthalene macrocycle bound to a thymine–thymine mismatch

The macrocyclic bis-naphthalene macrocycle (2,7-BisNP), belonging to the cyclobisintercalator family of DNA ligands, recognizes T–T mismatch sites in duplex DNA with high affinity and selectivity, as evidenced by thermal denaturation experiments and NMR titrations. The binding of this macrocycle to an 11-mer DNA oligonucleotide containing a T–T mismatch was studied using NMR spectroscopy and NMR-restrained molecular modeling. The ligand forms a single type of complex with the DNA, in which one of the naphthalene rings of the ligand occupies the place of one of the mismatched thymines, which is flipped out of the duplex. The second naphthalene unit of the ligand intercalates at the A-T base pair flanking the mismatch site, leading to encapsulation of its thymine residue via double stacking. The polyammonium linking chains of the macrocycle are located in the minor and the major grooves of the oligonucleotide and participate in the stabilization of the complex by formation of hydrogen bonds with the encapsulated thymine base and the mismatched thymine remaining inside the helix. The study highlights the uniqueness of this cyclobisintercalation binding mode and its importance for recognition of DNA lesion sites by small molecules